In the proposed work we plan to continue our studies on the action of glucocorticoids (dexamethasone) on the structure and function of hepatic cellular organelles. We intend to extend the investigation of hormonal effects on endoplasmic reticulum membrane biogenesis by studying the incorporation of H3-leucine into membrane proteins and C14-glycerole into membrane lipids in normal, adrenalectomized, and adrenalectomized rats given a single injection of dexamethasone. In these studies the endoplasmic reticulum is sub-fractionated into rough and smooth microsomes and purified membranes prepared from the microsomal sub-fractions. Further work will be performed to measure leucine incorporation into specific proteins which are isolated from the purified membranes prepared from the microsomal sub-fractions. Further work will be performed to measure leucine incorporation into specific proteins which are isolated from the purified rough and smooth microsomal membranes by electrophoresis. In addition, alterations in amounts of a microsomal marker enzyme (glucose-6-phosphatase) will be determined for the total hepatic homogenate, smooth and rough microsomes, and purified membranes of hepatic smooth and rough microsomes from normal, adrenalectomized, and dexamethasone-treated adrenalectomized rats. In order to correlate the biochemical results with alterations in the morphology of hepatocytes, a morphometric analysis of the fine structure of hepatocytes from dexamethasone-treated adrenalectomized rats will be made. Particular emphasis will be placed on the amount of hepatic rough and smooth endoplasmic reticulum in normal, overnight, fasted adrenalectomized animals, and adrenalectomized rats treated with dexamethasone. Further studies will be carried out on livers from hormonally stimulated rats which have received cycloheximide or actinomycin. It will be determined if the liver is capable of responding to glucocorticoid by proliferating smooth endoplasmic reticulum and depositing glycogen in the presence of the above inhibitors.